Despite aggressive marketing by makers of different diabetes drugs, and a steady stream of “new generation” treatments in recent years, a recent study suggests that there may be little difference in the effectiveness between a number of different classes of drugs designed to lower glucose levels, potentially exposing individuals to an increased risk of side effects or additional expenses associated with newer treatments.

Researchers from Australia, Greece, Canada and New Zealand published a study in the Journal of the American Medical Association (JAMA) on July 19, indicating that there is little difference in the effectiveness of drugs like Onglyza, Januvia, metformin, Actos, Precose, Glyset and sulfonylureas, with metformin being the most effective.

The study involved an analysis of 301 clinical trials, 177 where the drugs were given alone, and 109 trials involving combinations of metformin and other drugs, and 29 trials involving metformin, sulfonylureas and a third drug combined. Overall, the studies involved about 120,000 patients. Researchers looked at thiazolidinediones, like Actos and Avandia; DPP-4 inhibitors, like Onglyza and Januvia; and alpha glucosidase inhibitors, like Precose and Glyset.

“Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes,” the researchers concluded. “All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.”

Diabetes Drug Health Concerns

The findings come at a time when several diabetes drugs are under close scrutiny due to the risks of side effects which can be severe and debilitating.

Consumer advocacy groups have criticized pharmaceutical companies in recent years for putting out too many different diabetes drugs, indicating that they are often not thoroughly tested, and do virtually the same thing as existing treatments. The groups have accused the company of trying to keep profit margins high, potentially at the expense of patient safety.

Januvia (sitagliptin) is one of Merck & Co’s best-selling drugs and top drugs currently on the market in the United States, which was introduced in 2006 and has grown to generate sales of about $4 billion per year. Janumet is another version of the medication, which combines Januvia and Metformin, generating an additional $1 billion for the company.

In recent years, the drug maker has faced a number of Januvia lawsuits alleging that inadequate warnings were provided about the risk of users developing pancreatic cancer, as well as other health concerns.

Onglyza (saxagliptin) was developed jointly by AstraZeneca and Bristol-Myers Squibb, but is now owned wholly by AstraZeneca. It was approved by the FDA in July 2009, for treatment of type 2 diabetes and has also quickly grown to become a blockbuster treatment. However, in recent years concerns have emerged about a link between Onglyza and heart failure, following the publication of a study, known as “SAVOR”, by the New England Journal of Medicine in 2013.

Following regulatory review, the FDA required the drug makers to add new warnings to the medication last month, and a growing number of individuals are now pursuing an Onglyza lawsuit against AstraZeneca, alleging that consumers and the medical community were not provided adequate warnings about the potential heart risks.

Actos (pioglitazone) is another of the drugs evaluated in this recent study, which was one of the most widely used type 2 diabetes drugs in the United States until about 2010. Although it quickly became a top seller, sales fell sharply after the medical community learned about a potential link between Actos and bladder cancer.

About 8,000 Actos lawsuits were filed against Takeda Pharmaceuticals by individuals who indicated they developed bladder cancer following use of the medication. While the drug maker has attempted to defend the safety of their diabetes treatment, a $2.4 billion Actos settlment was reached in April 2015, following several multi-million dollar jury awards returned in individual cases that went to trial.

Some consumer watchdog groups, like Public Citizen, say that the only reason many of the new drugs are created is because the patents on the old drugs expire and the price drops in the face of generic competition. This results in companies rushing new diabetes drug formulations to the market in order to maximize profits, while often failing to conduct adequate clinical trials and research on potential side effects.

Invokana (canagliflozin) and Farxiga (dapagliflozin) are each members of a new class of diabetes drugs introduced in recent years, known as sodium-glucose co-transporter 2 (SGLT2) inhibitors. These drugs work in a different way from other diabetes treatments, impacting the normal function of the kidney. Although the effectiveness of Invokana and Farxiga were not evaluated in this latest study, questions about whether the drugs provide any benefits over other treatments have emerged since the drugs were aggressively marketed immediately after hitting the market, and quickly rose to become top sellers.

Like other new diabetes treatments, a series of serious safety risks have been linked to side effects of Invokana and Farxiga as more consumer-data is received, including a risk of diabetic ketoacidosis, kidney failure and other serious health problems.

Dozens of Invokana lawusits and Farxiga lawsuits are now being pursued in courts nationwide, raising similar allegations that the drug makers placed their desire for profits before consumers safety by pushing the drugs on the market too quickly, after only undergoing cursory clinical trials, and without warning consumers and the medical community about the potential health risks.